Difficulties in The Dietary Management of a Girl with Two Diseases Requiring a Special Diet

Abstract 3-Methylcrotonylglycinuria (3-MCG) is an autosomal recessive inborn error of leucine metabolism caused by the deficiency of 3-methylocrotonyl-CoA carboxylase (3-MCC deficiency). It is the most commonly detected organic aciduria in newborn screening conducted by tandem mass spectrometry (MS/MS) [1, 2]. The clinical phenotype is heterogeneous, ranging from asymptomatic to acute metabolic decompensations [3, 4]. Although at least in severe cases and in acute life threatening episodes limiting natural protein intake (particularly leucine) together with high caloric intake during catabolic periods is required, the need for specific dietary management often seems questionable [2]. In contrast with the 3-MCC deficiency, in diabetes mellitus type 1 (DM1) a diet based on carbohydrate and protein-fat exchangers is beyond dispute. However, as DM1 is quite a common disease, it may occur in a single patient with a rare disease, such as 3-MCC deficiency.

erefore, during hospitalization, urine organic acid analysis, by means of the GC-MS method was ordered and revealed an excessive increase of 3-hydroxyisovaleric acid, 3-methylcrotonylglycine and severe ketonuria.
is con rmed the diagnosis of the 3-MCC de ciency. Subsequent biochemical analysis showed a high level of plasma glutamine (951 μmol/L) and a decreased concentration of free and total carnitine (12 and 24 µmol/L, respectively). Consequently, in addition to the diet based on the carbohydrate exchange system, the medical nutrition therapy for 3-MCC de ciency was introduced [5]. e intake of natural protein, including leucine (up to 70-40 mg /kg bw), was reduced. e protein replacement leucine-free formula at a dose of 10 g/day was added to the diet. Oral supplementation with L-carnitine at a dose of 300 mg per day was introduced. A er obtaining the normalisation of biochemical parameters, the patient was discharged home.
At the age of 4 years and 5 months the girl was admitted to hospital due to metabolic decompensation caused by a gastro-intestinal infection. Her treatment began with a continuous infusion of 10% glucose, initially at a rate of 80 ml/h and then 55 ml/h, so the total daily energy intake (from food and intravenous glucose) amounted to 1200-1300 kcal. After the disappearance of vomiting and the return to oral nutrition, recommendations prior to infection were applied again. Information about the current difficulties in the implementation of dietary recommendations, especially regarding the requirements for 3MCC deficiency (refusal of formula intake) were obtained from the interview with the child's mother. e parents were afraid of hyperglycemia, hence they did not follow the recommendations on the use of leucine-free formula in 2-3 doses dissolved in fruit juice. Also, the increase in the calorie intake during the infection, recommended due to 3MCC de ciency, was considered by the parents a risk of the exacerbation of diabetes. Re-training for the parents was conducted in order to explain the principles of the management of each of the two disorders. Table I shows the content of energy, natural protein, the equivalent of protein and leucine in the diet of the girl during the observation period.

DISCUSSION
Early detection of inborn errors of metabolism (IEM) by newborn screening ensures that appropriate treatment is conducted early enough to prevent serious complications. It happens that the parents of children with 3-MCC de ciency, detected in NBS, dispute the validity of the diagnosis and the treatment when observing the asymptomatic disease and normal development of the baby. e importance and the consequences of parental noncompliance with the recommended treatment for a 19-month old girl with 3-MCC de ciency were described by Ficicioglu and Payan [6]. In the case described above, the parents' lack of understanding of the risks brought on by the disease and the di erences in dealing with situations that are o en initially asymptomatic was the cause of acute metabolic decompensation. e coexistence of two genetically determined diseases in a single patient is rarely recognised. Burlina et al. [7] reported a case of a boy diagnosed with DM1 at the age of 26 months, who presented with impaired walking, dysphagia and axial hypotonia identi ed 6 months later during an acute infection caused by glutaric aciduria type 1. e dietary treatment of inborn errors of metabolism, including 3-MCC de ciency, requires limiting the consumption of many foods, including high-protein food. For children aged 4-7, a safe intake of leucine ranges from 35 to 65 mg/kg bw. A supplementation with a mixture of essential (excluding leucine), and nonessential amino acids to maintain a positive balance of protein and to provide optimal growth and development is necessary [5]. e dietary imbalance described in the case reported could lead to the lack of metabolic control, and in the long-term could negatively a ect the patient's development. In order to reach the adequate amount of leucine in everyday diet, knowledge of the food composition and the calculation of the nutritional value of the total diet is necessary. e recommendations in 3-MMC de ciency and DM1 are quite opposite, at least in catabolic conditions. In 3-MCC de ciency, there is a need for high caloric intake, so intravenous and oral glucose is necessary, but in the DM1 -such management should be avoided. e course of the illness and the prognosis for the future depend on the good cooperation between the parents of the child with IEM and the medical team, or also the dietitian, in case a speci c diet is required.

CONCLUSION
is study demonstrates that two diseases requiring a speci c dietary management diagnosed in one child may be a huge challenge for both the medical team, as well as the child's parents. e authors show a case report of a patient with two coexisting diseases -3-MCC de ciency and DM1. Di culties in the dietary management of such a patient require regular, long-term monitoring with close cooperation between the patient's parents and a dietitian.